Autophagy refers to the process involving the decomposition of intracellular components via lysosomes. Autophagy plays an important role in maintaining and regulating cell homeostasis by degrading intracellular components and providing degradation products to cells. In vivo, autophagy has been shown to be involved in the starvation response, intracellular quality control, early development, and cell differentiation. Recent studies have revealed that autophagy dysfunction is implicated in neurodegenerative diseases and tumorigenesis. In addition to the discovery of certain disease-causing autophagy-related mutations and elucidation of the pathogenesis of conditions resulting from the abnormal degradation of selective autophagy substrates, the activation of autophagy is essential for prolonging life and suppressing aging. This article provides a comprehensive review of the role of autophagy in health, physiological function, and autophagy-related disease.

Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis.

Inflammatory bowel disease (IBD) is an idiopathic chronic and recurrent condition that comprises Crohn’s disease and ulcerative colitis. A pancreatic lesion is one of the extraintestinal lesions in patients with IBD. Acute pancreatitis is the representative manifestation, and various causes of pancreatitis have been reported, including those involving adverse effects of drug therapies such as 5-aminosalicylic acid and thiopurines, gall stones, gastrointestinal lesions on the duodenum, iatrogenic harm accompanying endoscopic procedures such as balloon endoscopy, and autoimmunity. Of these potential causes, autoimmune pancreatitis (AIP) is a relatively newly recognized disease and is being increasingly diagnosed in IBD. AIP cases can be divided into type 1 cases involving lymphocytes and IgG4-positive plasma cells, and type 2 cases primarily involving neutrophils; the majority of AIP cases complicating IBD are type 2. The association between IBD and chronic pancreatitis, exocrine pancreatic insufficiency, pancreatic cancer, etc. has also been suggested; however, studies with high-quality level evidence are limited, and much remains unknown. In this review, we provide an overview of the etiology of pancreatic manifestation in patients with IBD.

Although primarily a respiratory illness, several studies have shown that COVID-19 causes elevation of liver enzymes and various gastrointestinal (GI) symptoms. The aim of this study was to undertake a systematic review and meta-analysis to determine whether the presence of gastrointestinal (GI) symptoms contributed toward COVID-19 severity, and identify the GI symptoms characteristic of severe COVID-19. We conducted a literature search of PubMed from December 1, 2019, to June 30, 2020, and identified all reports with GI symptoms reported. A meta-analysis comparing the severity of COVID-19 with the presence of liver enzyme elevation and GI symptoms was performed using RevMan version 5.4. Pooled data from 15,305 unique reverse transcriptase-polymerase chain reaction positive COVID-19 patients from 44 studies were analyzed. We found that the severe COVID-19 patients significantly had abdominal pain compared to the non-severe COVID-19 patients (OR = 2.70, 95% CI 1.17-6.27, Z = 2.32, p = 0.02, I 2 = 0%) by analyzed 609 patients of 4 studies who reported both abdominal pain and COVID-19 severity. However, there was no significant difference in the incidence of diarrhea, nausea, or vomiting between the two groups. Thus, this systematic review and meta-analysis demonstrated that abdominal pain could be characteristic of severe COVID-19 infections. Compared with other viral infections that primarily infect the respiratory system, patients with COVID-19 have a slightly lower frequency of diarrheal symptoms with abdominal pain. However, to confirm this, further studies with COVID-19 patients across various countries and ethnicities are required.

Autophagy, an intracellular degradation mechanism, has many immunological functions and is a constitutive process necessary for maintaining cellular homeostasis and organ structure. One of the functions of autophagy is to control the innate immune response. Many studies conducted in recent years have revealed the contribution of autophagy to the innate immune response, and relationships between this process and various diseases have been reported. Inflammatory bowel disease is an intractable disorder with unknown etiology; however, immunological abnormalities in the intestines are known to be involved in the pathology of inflammatory bowel disease, as is dysfunction of autophagy. In Crohn’s disease, many associations with autophagy-related genes, such as ATG16L1, IRGM, NOD2, and others, have been reported. Abnormalities in the ATG16L1 gene, in particular, have been reported to cause autophagic dysfunction, resulting in enhanced production of inflammatory cytokines by macrophages as well as abnormal function of Paneth cells, which are important in intestinal innate immunity. In this review, we provide an overview of the autophagy mechanism in innate immune cells in inflammatory bowel disease.

The relevance of endoscopic monitoring of ulcerative colitis (UC) has been translated into the new concept of “mucosal healing (MH)” as the therapeutic goal to achieve because a large amount of scientific data have revealed the favorable prognostic value of a healed mucosa in determining the clinical outcome of UC. Recent interest in MH has skewed toward not only endoscopic remission but also histological improvement (so called histological MH). However, we should recognize that there have been no prospectively validated endoscopic scoring systems of UC activity in previous clinical trials. Artificial intelligence (AI)‐assisted endoscopy has been developed for gastrointestinal cancer surveillance. Recently, several AI‐assisted endoscopic systems have been developed for assessment of MH in UC. In the future, the development of a new endoscopic scoring system based on AI might standardize the definition of MH. Therefore, “The road to an exact definition of MH in the treatment of UC has begun only now”.

Osteopontin (OPN) is involved in a variety of biological processes, including bone remodeling, innate immunity, acute and chronic inflammation, and cancer. The expression of OPN occurs in various tissues and cells, including intestinal epithelial cells and immune cells such as macrophages, dendritic cells, and T lymphocytes. OPN plays an important role in the efficient development of T helper 1 immune responses and cell survival by inhibiting apoptosis. The association of OPN with apoptosis has been investigated. In this review, we described the role of OPN in inflammatory gastrointestinal and liver diseases, focusing on the association of OPN with apoptosis. OPN changes its association with apoptosis depending on the type of disease and the phase of disease activity, acting as a promoter or a suppressor of inflammation and inflammatory carcinogenesis. It is essential that the roles of OPN in those diseases are elucidated, and treatments based on its mechanism are developed.

Several reports have indicated a possible link between decreasing plasma levels of vitamin K and bone mineral density. It has been suggested that intestinal bacteria contribute to maintenance of vitamin K. Several factors are involved in the reduction of vitamin K in patients with Crohn’s disease (CD). We aimed to assess the relationship between gut microbiota and alternative indicators of vitamin K deficiency in patients with CD. We collected the feces of 26 patients with clinically inactive CD. We extracted 16S rRNA from the intestinal bacteria in the feces and amplified it by polymerase chain reaction. The generated polymerase chain reaction product was analyzed using a 16S metagenomic approach by Illumina Miseq platform. Serum undercarboxylated osteocalcin concentration was used as an alternative indicator of vitamin K deficiency. There was a significant negative correlation between serum undercarboxylated osteocalcin and mean Chao1 index in cases of low activity. The diversity of the gut microbiota was significantly lower, and Ruminococcaceae and Lachnospiraceae were significantly decreased in the vitamin K-deficient group in comparison to the vitamin K-normal group. Taken together, these data suggested the significance of investigating the gut microbiota even in patients with clinically inactive CD for improving patients’ vitamin K status.